HGF-mediated Up-regulation of PHLDA2 Is Associated With Apoptosis in Gastric Cancer

Background/Aim: Expression of pleckstrin homology-like domain family A member 2 (PHLDA2) has been reported to be suppressed or activated in several cases of malignant tumors. However, its apoptotic regulatory mechanism and role in gastric cancer are not understood. This study examined the role of PHLDA2 in apoptosis in gastric cancer. Materials and Methods: We used cell culture, western blotting, semiquantitative reverse transcription polymerase chain reaction, MTT assays, and PHLDA2 knockdown with short hairpin RNA (shRNA). Results: To identify the pathway associated with HGF-induced PHLDA2 up-regulation, the cells were treated with PI3-kinase inhibitor (LY294002), MEK inhibitor (PD098059), or p38 inhibitor (SB203580) and then analyzed by western blotting. HGF-mediated changes in PHLDA2 protein levels were only decreased by LY294002. PHLDA2-shRNA cells showed decreased levels of p53 and increased levels of pAKT. Furthermore, HGF-induced cell proliferation and in vitro invasion were increased in PHLDA2 knockdown cells and HGF-induced cell apoptosis was increased in PHLDA2 knockdown cells. Conclusion: PHLDA2 plays a role in gastric cancer tumorigenesis by inhibiting apoptosis through the PI3K/AKT pathway.